Page 78 - Book Hosokawa Nanoparticle Technology Handbook

FUNDAMENTALS CH. 2 STRUCTURAL CONTROL OF NANOPARTICLES
and had a self-film-formability in water was developed matrix. They have been used chiefly in the hyperthermia
as a coating material (Table 2.1.1(h)) [12]. This com- treatment of cancer and, in some cases, for magnetic
posite latex consisted of a terpoly(EA/MMA/HEMA) field-assisted targeting of nanoparticles. For diagnostic
core and a non-crosslinked, thermosensitive poly(N- purposes, they were used in magnetic resonance imag-
isopropylacrylamide (NIPAAm)) shell. When com- ing (MRI) as contrast enhancing agents for the purpose
pared to homogeneous latexes with no poly(NIPAAm) of cancer diagnosis, targeted molecular imaging, hyper-
shell, the composite latexes reduced the production of fusion region visualization, cell labeling in T-cell-based
poorly coated particles and the particle size depend- therapy, and for detection of angiogenesis, apoptosis,
ence of polymer yield when the coating operation was and gene expression. PEG or oxidized starch
done at a temperature where poly(NIPAAm) shells (Table 2.1.1(i)) [14] as a hydrophilic surface-modifier,
were able to swell, i.e., below the lower critical solu- antibodies, FITC-labeled Tat peptide (Table 2.1.1(j))
tion temperature (LCST: 32°C) of poly(NIPAAm). [15] or the Annexin V protein (Table 2.1.1(k)) [16] as a
Further, the surface-layer constructed with the compos- specific targeting agent, and folic acid (Table 2.1.1(l))
ite latex particles also exhibited a self-film-formability [17] or transferrin (Table 2.1.1(m)) [18] as a ligand of
in water at 37°C, resulting from shrinkage of the the receptors overexpressed in tumor cells have been
poly(NIPAAm) shells in the membrane at temperatures used as surface molecules.
above the LCST. Thus, the coated particles exhibited a
rapid release of drug at low temperatures, and a sup-
pressed release at high temperatures (negative thermo- 2.1.5 Simple organic nanoparticles
sensitivity).
The composite latexes composed of a hydrophobic The active agents are often incorporated or dispersed in
poly(EA/MMA) core and a thermosensitive poly the matrix to control or suppress their release. Polymers
(NIPAAm) shell (Table 2.1.1(h)) [13] were synthe- [19–27] and waxes or lipids [28–34] have been widely
sized by a semi-continuous two-stage emulsion poly- used as matrix materials. Table 2.1.1(n–w) shows vari-
merization technique. The poly(NIPAAm) shell was ous matrix nanoparticles that have recently been inves-
cross-linked with methylene bisacrylamide. The tigated for delivery of active agents; they are often for
microcapsules with thermosensitive coats were pre- doxorubicin, an anticancer drug, whose liposomes are
pared using a spouted bed coater assisted with a draft on the market as Doxil TM (Alza Corp.). In these
tube and bottom-spray, known as the Wurster process. nanoparticles, biodegradable polymers, such as PLA
The key structure of the microcapsules designed here [19], PLGA, poly( -caprolactone) [20], chitosan,
was its composite coat, consisting of nanosized thermo- PACA, poly(lysine), and poly(aspartic acid) [21], are
sensitive hydrogels dispersed in a thermo-insensitive used as the polymeric matrix. The matrixes, consisting
polymeric matrix (ethylcellulose). At high temperatures, of artificial polymers or naturally occurring polymers
therefore, the poly(NIPAAm)-gel domains in the such as albumin and gelatin have also been used in
microcapsule membranes shrank, probably leading to nanoparticles for gene delivery. The polymers used
the creation of many voids in the membranes. therein are often cationic to enhance association with
Consequently, the water-permeability increased as if a anionic cell surfaces and/or DNAs.
molecular valve had been opened. Owing to the voids The Gd-DTPA-loaded chitosan nanoparticles (Gd-
thus formed, the drug release rate at high tempera- nanoCPs) for gadolinium neutron capture therapy
tures became higher than that at low temperatures (Gd-NCT) were reported (Table 2.1.1(t)) [25–27].
(positive thermo-sensitivity). Gd-nanoCPs were prepared by a novel emulsion-
droplet coalescence technique. Gd-nanoCPs with the
highest Gd content, which were obtained using 100%
2.1.4 Simple inorganic nanoparticles deacetylated chitosan in 15% Gd-DTPA aqueous
solution, were 452 nm in diameter and had a Gd-
Recently, inorganic nanoparticles that interact with DTPA content of 45%. Gd-DTPA loaded onto Gd-
biological systems have attracted widespread interest nanoCPs was barely released in PBS (1.8%) over
in biology and medicine. Such nanoparticles are 7 days despite the high water solubility of Gd-DTPA.
thought to have potential as novel intravascular probes In contrast, 91% of Gd-DTPA was released in plasma
for both diagnostic (e.g., imaging) and therapeutic over 24h. When Gd-nanoCPs were intratumorally
purposes (e.g., drug delivery). Critical issues for suc- injected, 92% of Gd-DTPA injected efficiently with-
cessful nanoparticle delivery include the ability to tar- out outflow was retained in the tumor tissue for 24 h,
get specific tissues and cell types and escape from the which was different from the case of Gd-DTPA solu-
biological particulate filter (RES). tion injection (only 1.2%). Thus, Gd-nanoCPs with a
Among inorganic materials, magnetite has been high content of water-soluble Gd-DTPA were suc-
investigated most widely for cancer therapy and diag- cessfully prepared by the emulsion-droplet coales-
nosis (Table 2.1.1(i–m)) [14–18]. Magnetite nanoparti- cence technique. Their high Gd content, releasing
cles were used directly or dispersed in the polymeric properties and ability for long-term retention of

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